Variant 7-22941909-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032581.4(HYCC1):c.*3680A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,008 control chromosomes in the GnomAD database, including 11,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 11754 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

HYCC1
NM_032581.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

HYCC1 (HGNC:24587): (hyccin PI4KA lipid kinase complex subunit 1) The protein encoded by this gene may play a part in the beta-catenin/Lef signaling pathway. Expression of this gene is down-regulated by beta-catenin. Defects in this gene are a cause of hypomyelination with congenital cataract (HCC). [provided by RefSeq, Oct 2008]

HYCC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 7-22941909-T-C is Benign according to our data. Variant chr7-22941909-T-C is described in ClinVar as [Benign]. Clinvar id is 359721.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYCC1	NM_032581.4 linkuse as main transcript	c.*3680A>G		3_prime_UTR_variant	11/11	ENST00000432176.7	NP_115970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYCC1	ENST00000432176.7 linkuse as main transcript	c.*3680A>G		3_prime_UTR_variant	11/11	1	NM_032581.4	ENSP00000403396		Q9BYI3-1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59799

AN:

151890

Hom.:

11741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.361

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.394

AC:

59848

AN:

152008

Hom.:

11754

Cov.:

AF XY:

0.393

AC XY:

29197

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.389

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.467

Gnomad4 EAS

AF:

0.506

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.390

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.387

Hom.:

1809

Bravo

AF:

0.396

Asia WGS

AF:

0.472

AC:

1623

AN:

3434

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypomyelination and Congenital Cataract

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.5

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over